The major causes of chronic renal failure in the United States include conditions affecting the glomerulus (e.g. diabetes, FSGS, hypertension, and inflammatory glomerular disease), while those causing acute renal failure involve the renal tubule through toxic and ischemic mechanisms. Both types of renal failure are associated with high mortality and cost to the Nation. The human genome project offers enormous opportunities to understand and develop new strategies for manipulating signaling pathways and structural protein complexes that will have potential therapeutic and diagnostic utility in kidney diseases. To take advantage of these opportunities this Renal Center will have a Molecular/Morphology Core and four individual research projects. The individual projects are derived in part from prior work previously supported by the Renal Center, and will focus on newly discovered and cloned molecules which regulate glomerular structure and function (Wiggins, Wang and Margolis/Kershaw), on protein:protein: lipid interactions as they become uncontrolled and uncoordinated in the hypoxic tubule (Weinberg/Shayman), and on signaling systems involved in tubulogenesis that may be important in tubular regeneration following injury (Dressler/Dixon). A major role of the Molecular/Morphology core will be the production of high quality libraries of various types (e.g. RNA, cDNA, yeast two hybrid, full length cDNA for mammalian expression) for the dissection of protein interactions of importance in the glomerulus, tubule and developing kidney. In order to create this Core we have had to identify additional support ($400,000 over 5 years) from a private donor and the Institution. Our goal is that this Molecular/Morphology Core will be a resource that will serve both the Center projects and other investigators in our Institution as well as the renal community at large through rapid dissemination of the libraries that are developed.